# Mechanisms Underlying Muscle Development and Maintenance in Drosophila

> **NIH NIH R01** · KANSAS STATE UNIVERSITY · 2021 · $220,304

## Abstract

PROJECT SUMMARY
Our prior work focused on understanding mechanisms that contribute to the development of a
stable, mature myotendinous junction (MTJ). Results obtained during the past funding cycle
identified essential roles for evolutionarily conserved proteins not just in the formation, but also in
the maintenance, of muscle-tendon interactions. Interestingly, continued maintenance of MTJ
formation is intimately linked to muscle homeostasis. The overall goal during the next funding
period is to understand how proteostasis is regulated in the context of cell homeostasis. The
inability to remove protein aggregates in non-dividing cells such as neurons or muscles is a key
factor in the development and progression of neurodegenerative diseases and myopathies and
is a cellular hallmark of aging cells. While protein aggregate diseases share common features, it
is widely assumed that the molecular pathways that lead to protein aggregation cannot be
explained by a single mechanism. In protein aggregation disease that cause myopathies, a
general trend has emerged in which aggregated proteins and organelles accumulate in regions
devoid of muscle tissue. However, the cellular and mechanical triggers that initiate Z-disk
disintegration and myofiber displacement are unclear. Here we employ mutations in conserved
Drosophila genes as an entry point to uncover cellular and molecular mechanisms that lead to
protein aggregation and ultimately cellular degeneration using muscle as a model cell type.
Overall, we expect to uncover unrecognized aspects of, including, but not limited to: uncovering
novel components that contribute to proteostasis; identifying muscle targets of kinase activity; and
determining how autophagy cooperates in the clearance of protein aggregates. A powerful
combination of genetic analysis, biochemistry, cell biology, and live imaging approaches will
address these questions. We expect that this project will fundamentally advance our
understanding of how protein degradation is regulated to prevent cellular degeneration and to
provide fresh insights into how protein aggregates can be effectively cleared to reduce disease
states.

## Key facts

- **NIH application ID:** 10454072
- **Project number:** 3R01AR060788-08S1
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Erika Rae Geisbrecht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $220,304
- **Award type:** 3
- **Project period:** 2012-08-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454072

## Citation

> US National Institutes of Health, RePORTER application 10454072, Mechanisms Underlying Muscle Development and Maintenance in Drosophila (3R01AR060788-08S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10454072. Licensed CC0.

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